Title

Decrease of Yellow Fever neutralizing antibody titers one year after vaccination is related to different NK cells repertoire in PLWH and non-HIV controls - ANRS12403

Presenter

Lara Esteves Coelho

Authors

A. da Silva Cazote¹, L. Nery da Silva Caldas¹, D. Granato da Costa Lima¹, D. Victalina de Almeida¹, J. Henrique Pilotto¹, S.M. Barbosa de Lima², A. de Souza Azevedo Soares², Y. da Silva Mendes², A. Bispo de Filippis³, M. Morata⁴, L. Gomes Pedro Brandão⁴, M. Dias⁴, S. Wagner Cardoso⁴, B. Grinsztejn⁴, L. Antônio Camacho⁵, L. Esteves Coelho⁴, F. Heloise Cortes¹, D. Scott-Algara⁶, C.B. Wagner Giacoia Gripp¹

Institutions

¹Oswaldo Cruz Institute - Oswaldo Cruz Foundation, Laboratory of AIDS and Molecular Immunology, Rio de Janeiro, Brazil, ²Biomanguinhos - Oswaldo Cruz Foundation, Laboratory of Virological Technology, Rio de Janeiro, Brazil, ³Oswaldo Cruz Institute - Oswaldo Cruz Foundation, Laboratory of Flavivirus, Rio de Janeiro, Brazil, ⁴National Institute of Infectious Diseases Evandro Chagas - Oswaldo Cruz Foundation, Rio de Janeiro, Brazil, ⁵National School of Public Health Sergio Arouca - Oswaldo Cruz Foundation, Rio de Janeiro, Brazil, ⁶Pasteur Institute, Paris, France

BACKGROUND: Yellow fever (YF) vaccine has been successfully used to control YF disease and prevent new outbreaks. The 17DD YF vaccine is considered a safe and highly effective vaccine in people living with HIV (PLWH), but the immunogenicity mechanisms are not completely understood. This study hypothesized that, despite HIV viral load (VL) suppression, PLWH could present reduced production and maintenance of YF-neutralizing antibodies (NAbs) and that NK cells different repertoire could participate in this process.
METHODS: This study was nested in a longitudinal study that investigated YF vaccine safety and immunogenicity in PLWH and non-HIV controls (CTRL). NK cells repertoire was evaluated in PLWH with baseline CD4⁺ T cell counts = 200 cells/mm³ and suppressed VL (n=25), and in CTRL (n=16), by flow cytometry, at pre-vaccination (Day 0), and at three moments post-vaccination (Days 5, 30 and 365). YF vaccine immunogenicity was evaluated by Nab levels measured through a micro plaque reduction neutralization test (µPRNT, cut-off = 1:100) at Days 30 and 365. For the analysis, all participants were grouped regardless HIV status and according to Nab titers at Day 365 as: low (>1:100 and < 1:500), moderate (=500 and <1000) and high (=1000).
RESULTS: YF vaccine resulted in protective Nab titers at Day 30 in all participants, which decreased after one year, regardless of HIV status or CD4⁺ T cells counts. Interestingly, the frequencies of NKp30⁺ and NKG2A⁺ NK cells were significantly lower at D0 among the low Nabs participants, compared to individuals having moderate and high NAbs titers (p<0,05). Such lower frequencies were significant in all the moments, compared to the moderate Nabs participants (p<0,05).
CONCLUSIONS: Although serological correlates of protection have not been established, higher YF NAbs titers plausibly indicate longer protection against disease. NKp30 is an important NK activation receptor while NKG2A is related to high responsive educated NK cells. Early activation of NK cells can engage pathways involving B cells response, wich leads to humoral immunity against viruses (due to infections or vaccine). Our results suggest that NK cell repertoire presented before vaccination could impact YF vaccine immunogenicity and long term duration of the NAbs protection.

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